The overall objective of this project is to define the nature of polypeptide, endocrine hormone interaction with normal and neoplastic hematopoietic cells and to purify and characterize the hematopoietic hormone acting on early human erythroid and pluripotent stem cells that is referred to as erythroid-potentiating activity (EPA). The specific aims are: (1)\to elucidate the interaction of polypeptide hormones with normal and neoplastic hematopoietic cells and to determine the pattern of erythropoietic stem-cell response to polypeptide hormones in various disease states, including dwarfism and diabetes; (2)\to correlate polypeptide hormone binding to hematopoietic cells with their physiological effects; (3)\to purify to homogeneity the glycoprotein hormone referred to as EPA produced by a unique human T-cell line available in our laboratory; and (4)\to chemically and biologically define the interaction of EPA with normal and neoplastic hematopoietic stem cells. In vitro clonal, hematopoietic, stem-cell assay technology will be used to determine the responsiveness of human T-lymphocyte precursors, erythropoietic stem cells, and multipotent stem cells to growth hormone, related peptides, and insulin in normal subjects and in disease states. The diseases to be studied include dwarfism, diabetes, and erythroleukemia and lymphoid leukemias. Polypeptide hormone binding to various normal and neoplastic hematopoietic cells will be analyzed. A human T-cell line, unique to our laboratory, produces a number of lymphokines and hematopoietic hormones. This cell line will be used to produce, purify, and characterize the glycoprotein hormone referred to as EPA, the primary early regulator of hematopoiesis in vitro. Biochemical techniques will be used to purify this hormone to homogeneity. The biology of the purified hormone will be studied by assessing its effects on various normal and neoplastic hematopoietic precursor cells and by determining its binding properties to these cells under various circumstances. The studies outlined should provide important information regarding the hormonal regulation of normal and malignant hematopoiesis in humans. (C)